TY - JOUR
AU - Forget, Antoine
AU - Martignetti, Loredana
AU - Puget, Stéphanie
AU - Calzone, Laurence
AU - Brabetz, Sebastian
AU - Picard, Daniel Joseph
AU - Montagud, Arnau
AU - Liva, Stéphane
AU - Sta, Alexandre
AU - Dingli, Florent
AU - Arras, Guillaume
AU - Rivera, Jaime
AU - Loew, Damarys
AU - Besnard, Aurore
AU - Lacombe, Joëlle
AU - Pagès, Mélanie
AU - Varlet, Pascale
AU - Dufour, Christelle
AU - Yu, Hua
AU - Mercier, Audrey L
AU - Indersie, Emilie
AU - Chivet, Anaïs
AU - Leboucher, Sophie
AU - Sieber, Laura
AU - Beccaria, Kevin
AU - Gombert, Michael
AU - Meyer, Frauke-Dorothee
AU - Qin, Nan
AU - Bartl, Jasmin
AU - Chavez, Lukas
AU - Okonechnikov, Konstantin
AU - Sharma, Tanvi
AU - Thatikonda, Venu
AU - Bourdeaut, Franck
AU - Pouponnot, Celio
AU - Ramaswamy, Vijay
AU - Korshunov, Andrey
AU - Borkhardt, Arndt
AU - Reifenberger, Guido
AU - Poullet, Patrick
AU - Taylor, Michael D
AU - Kool, Marcel
AU - Pfister, Stefan
AU - Kawauchi, Daisuke
AU - Barillot, Emmanuel
AU - Remke, Marc
AU - Ayrault, Olivier
TI - Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling.
JO - Cancer cell
VL - 34
IS - 3
SN - 1535-6108
CY - Cambridge, Mass.
PB - Cell Press
M1 - DKFZ-2018-01521
SP - 379 - 395.e7
PY - 2018
AB - The current consensus recognizes four main medulloblastoma subgroups (wingless, Sonic hedgehog, group 3 and group 4). While medulloblastoma subgroups have been characterized extensively at the (epi-)genomic and transcriptomic levels, the proteome and phosphoproteome landscape remain to be comprehensively elucidated. Using quantitative (phospho)-proteomics in primary human medulloblastomas, we unravel distinct posttranscriptional regulation leading to highly divergent oncogenic signaling and kinase activity profiles in groups 3 and 4 medulloblastomas. Specifically, proteomic and phosphoproteomic analyses identify aberrant ERBB4-SRC signaling in group 4. Hence, enforced expression of an activated SRC combined with p53 inactivation induces murine tumors that resemble group 4 medulloblastoma. Therefore, our integrative proteogenomics approach unveils an oncogenic pathway and potential therapeutic vulnerability in the most common medulloblastoma subgroup.
LB - PUB:(DE-HGF)16
C6 - pmid:30205043
DO - DOI:10.1016/j.ccell.2018.08.002
UR - https://inrepo02.dkfz.de/record/137641
ER -